Temperature-sensitive recombinant mutant viruses and a process for producing same

Abstract

A method and resulting temperature sensitive (ts) recombinants which may be produced by modifying wild-type influenza A viruses by utilization of chemically mutagenized donor viruses possessing ts lesions and shut off temperatures in the area 37 DEG -38 DEG C. Such a recombinant virus has been produced that contains the surface H3 antigen of influenza A/Hong Kong/1968 (H3N2) virus and a temperature-sensitive (ts) lesion derived from a ts mutant of influenza A/Great Lakes/1965 (H2N2) virus. Additional donor viruses include influenza A/Hong Kong/1968-ts-1[A], influenza A double recombinant 10B, and influenza A/Hong Kong/1968-ts-1[E]. When utilized as a vaccine, these temperature-sensitive recombinant viruses have the facility to develop only mild symptoms, but the infection induces complete resistant to influenzal disease produced by challenge with a virulent wild-type virus. The temperature-sensitive donor mutant is prepared chemically by growth of the virus in the presence of 5-fluorouracil (5-FU).

We claim: 
     
       1. A composition consisting of a virus and a compatible carrier wherein said virus consists of a temperature-sensitive (ts) recombinant mutant virus produced by growth of an influenza A virus in the presence of 5-fluorouracil to produce a chemically mutagenized and temperature-sensitive virus which is the donor of a defined genetic defect and which is mated with a virulent wild-type A virus of a different antigenic type to produce the recombinant mutant virus. 
     
     
       2. The composition according to claim 1 wherein the temperature-sensitive donor virus is influenza A/Hong Kong/1968-ts-1(A). 
     
     
       3. The composition according to claim 1 wherein the temperature-sensitive donor virus is influenza A Double recombinant 10B. 
     
     
       4. The composition according to claim 1 wherein the temperature-sensitive donor virus is influenza A/Hong Kong/1968-ts-1(E). 
     
     
       5. A method of producing a temperature-sensitive (ts) recombinant mutant virus which has a shut-off temperature of about 37°-38° C which comprises growing an influenza A virus in the presence of 5-fluorouracil to produce a donor virus possessing a temperature-sensitive genetic defect and mating said donor virus with a virulent wild-type A virus of a different antigenic type to produce a ts recombinant mutant virus of the new antigenic type.